This study is designed to ascertain a relatively large number of maternal and paternal half-siblings of prospositi affected by anencephaly and spina bifida, within a large human population. We will then determine the risk of recurrence of these congenital malformations among those half-sibs. The method which will be used to locate half- sibs of prospositi has been tried and proven successful. Evidence of malformations among the identified half-sibs will be sought in birth records, fetal death records and hospital records. Under the category of anencephaly and spina bifida we will incorporate all neural tube closure defects including encephalocele, meningocele, meningomyelocele and myelocele. The recurrence risk among full sibs of index cases is being independently determined through family studies covering a similar time period and geographic population. The recurrence risks in full sibs and half-sibs will be compared. The results will then be used to test the validity of the available hypotheses of causation of these malformations in man - polygenic inheritance, extranuclear inheritance, and recurrence of environmental factors.